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Analysis of the interaction between the ORF42 and ORF55 proteins encoded by Kaposi’s sarcoma-associated herpesvirus

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Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) causes Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman disease. The tegument is a structure that is unique to herpesviruses that includes host and viral proteins, including the viral ORF42 and ORF55 proteins. Alphaherpesvirus tegument proteins have been well studied, but much is unknown regarding KSHV. Here, we report an interaction between the ORF42 and ORF55 proteins. ORF55 interacted with and recruited ORF42 from the nucleus to the cytoplasm. When ORF42 and ORF55 were expressed simultaneously in cultured cells, the expression level of these two viral proteins was higher than when either was expressed independently. ORF55, but not ORF42, was polyubiquitinated, suggesting that an unidentified regulatory mechanism may be present. A recombinant virus with an ectopic stop codon in ORF42 exhibited normal replication of genomic DNA, but fewer virus particles were released with the recombinant than with the wild-type virus. A unique R136Q mutation in ORF42, which is found in a KSHV strain that is prevalent on Miyako Island, Okinawa Prefecture, Japan, further increased the expression of ORF42 and ORF55 when these proteins were expressed simultaneously. However, the ORF42 R136Q mutation did not affect the localization pattern of ORF42 itself or of ORF55. In addition, experiments with a recombinant virus possessing the ORF42 R136Q mutation showed lower levels of production of the mutant virus than of the wild-type virus, despite similar levels of genome replication. We suggest that the R136Q mutation in ORF42 plays an important role in ORF55 protein expression and virus production.

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No publicly available datasets were included in this study.

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Acknowledgements

The BAC16 KSHV clone was a gift from Kevin Brulois and Jae U. Jung (USC, USA). We thank Gregory A. Smith (Northwestern University, USA) for Escherichia coli strain GS1783, and Nikolaus Osterrieder (Cornell University, USA) for the plasmid pEP-KanS. K.K. was supported by a Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan. We would like to thank Editage (www.editage.jp) for English language editing.

Funding

This study was supported by a research grant from the Okinawa Medical Science Research Foundation (to Kazushi Kuriyama).

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Authors and Affiliations

  1. Department of Virology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan

    Kazushi Kuriyama, Tadashi Watanabe & Shinji Ohno

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  1. Kazushi Kuriyama
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  2. Tadashi Watanabe
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  3. Shinji Ohno
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Contributions

All authors contributed to the study conception and design. Experiments were conducted by Kazushi Kuriyama and Tadashi Watanabe. All authors interpreted the data. Kazushi Kuriyama wrote, and all authors commented on, the first draft of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shinji Ohno.

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Kuriyama, K., Watanabe, T. & Ohno, S. Analysis of the interaction between the ORF42 and ORF55 proteins encoded by Kaposi’s sarcoma-associated herpesvirus. Arch Virol 169, 98 (2024). https://doi.org/10.1007/s00705-024-06021-7

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